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Notch signaling defines an evolutionarily ancient cell interaction mechanism, which plays a fundamental role in metazoan development. Signals exchanged between neighboring cells through the Notch receptor can amplify and consolidate molecular differences, which eventually dictate cell fates. Thus, Notch signals control how cells respond to intrinsic or extrinsic developmental cues that are necessary to unfold specific developmental programs. Notch activity affects the implementation of differentiation, proliferation, and apoptotic programs, providing a general developmental tool to influence organ formation and morphogenesis.
The building of an organism from a single cell to a multicellular three-dimensional structure of characteristic shape and size is the result of coordinated gene action that directs the developmental fate of individual cells. The acquisition of different cell fates orchestrates an intricate interplay of cell proliferation, migration, growth, differentiation, and death, elaborating and bringing together cellular ensembles in a precise manner. Intrinsic, cell-autonomous factors as well as nonautonomous, short-range and long-range signals guide cells through distinct developmental paths. Frequently, an organism uses the same signaling pathway within different cellular contexts to achieve unique developmental goals. How intrinsic and extrinsic factors are integrated in ontogeny to specify cell fates defines the central question of developmental biology.
Notch signaling is an evolutionarily conserved mechanism that is used by metazoans to control cell fates through local cell interactions. The realization that this signaling mechanism controls an extraordinarily broad spectrum of cell fates and developmental processes (in organisms ranging from sea urchins to humans) resulted in a veritable explosion of Notch-related studies in the past decade. Our intention here is not to review all the systems and cellular events that depend on this mechanism, because several reviews adequately cover these many issues (1-7). Instead, we present some general developmental features emerging from collective studies in vertebrate and invertebrate experimental systems as well as consider certain mechanistic aspects of Notch signaling. These studies make it apparent that signals transmitted through the Notch receptor, in combination with other cellular factors, influence differentiation, proliferation, and apoptotic events at all stages of development. Thus, Notch signaling appears to function as a general developmental tool that is used to direct cell fate and, consequently, to build an organism.
Elements of Notch Signaling
The gene encoding the Notch receptor was discovered in flies...